主权项 |
1. A method comprising administering to a subject with cancer an isolated antibody or antigen-binding fragment thereof that specifically binds to semaphorin-4D (SEMA4D), and an effective amount of an antibody or antigen-binding fragment thereof that inhibits an immune checkpoint blockade;
wherein the cancer is a solid tumor, and wherein SEMA4D is expressed by tumor cells of the solid tumor or by cells in the tumor microenvironment; and wherein the antibody or antigen-binding fragment thereof that specifically binds to SEMA4D comprises a variable heavy chain (VH) comprising VHCDRs 1-3 comprising SEQ ID NO: 6, 7, and 8, respectively, and a variable light chain (VL) comprising VLCDRs 1-3 comprising SEQ ID NO: 14, 15, and 16, respectively, and the antibody that inhibits the immune checkpoint blockade inhibitor is an anti-Programmed Cell Death 1 (PD-1) antibody, an anti-Programmed Death-Ligand 1 (PD-L1) antibody, an anti-Lymphocyte Activation Gene 3 (LAG3) antibody, an anti-B7-H3 antibody, an antigen-binding fragment thereof, or a combination thereof, or wherein the antibody or antigen-binding fragment thereof that specifically binds to SEMA4D comprises a variable heavy chain (VH) comprising SEQ ID NO:9 and a variable light chain (VL) comprising SEQ ID NO:17, and the antibody that inhibits the immune checkpoint blockade inhibitor is an anti-cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) antibody, an anti-Programmed Cell Death 1 (PD-1) antibody, an anti-Programmed Death-Ligand 1 (PD-L1) antibody, an anti-Lymphocyte Activation Gene 3 (LAG3) antibody, an anti-B7-H3 antibody, an antigen-binding fragment thereof, or a combination thereof. |